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Structure-Function Analyses of a Keratin Heterotypic Complex Identify Specific Keratin Regions Involved in Intermediate Filament Assembly
- Structure-Function Analyses of a Keratin Heterotypic Complex Identify Specific Keratin Regions Involved in Intermediate Filament Assembly
- Lee, Chang-Hun; Kim, Min-Sung; Li, Shuang; Leahy, Daniel J.; Coulombe, Pierre A.
- DGIST Authors
- Lee, Chang-Hun
- Issue Date
- Structure, 28(3), 355-362.e4
- Article Type
- Author Keywords
- intermediate filament; keratinocyte; skin; epithelium; self-assembly; crystal structure; epidermolysis bullosa simplex; structural protein; cytoskeleton; 2B domain
- EPIDERMOLYSIS-BULLOSA SIMPLEX; 2B ROD DOMAIN; COILED-COIL; MOLECULAR ARCHITECTURE; CRYSTAL-STRUCTURE; ATOMIC-STRUCTURE; POINT MUTATIONS; CROSS-LINKING; VIMENTIN; DISEASE
- Intermediate filaments (IFs) provide vital mechanical support in a broad array of cell types. Interference with this role causes cell fragility and accounts for a large number of human diseases. Gaining an understanding of the structure of IFs is paramount to understanding their function and designing therapeutic agents for relevant diseases. Here, we report the 2.6-Å resolution crystal structure of a complex of interacting 2B domains of keratin 5 (K5) and K14. K5 and K14 form a long-range, left-handed coiled coil, with participating α helices aligned in parallel and in register. Follow-up mutagenesis revealed that specific contacts between interacting 2B domains play a crucial role during 10-nm IF assembly, likely at the step of octamer-octamer association. The resulting structural model represents an atomic-resolution visualization of 2B-2B interactions important to filament assembly and provides insight into the defects introduced by mutations in IF genes associated with human skin diseases. © 2020 Elsevier Ltd
Our understanding of the assembly and structure of 10-nm keratin intermediate filaments remains superficial. Here, Lee et al. report on the crystal structure of 2B domain heterocomplexes from keratin 5 and keratin 14. Mutagenesis studies highlight 2B-2B molecular interactions that are poised to sustain filament elongation during polymerization. © 2020 Elsevier Ltd
- Cell Press
- Related Researcher
Biointerface Structure and Skin Lab
Structure-Function relationship of cytoskeletal proteins and membrane proteins; Structure-based design of biomolecules and drugs; Development of drug delivery system in skin
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